Adaptimmune Ltd & Immunocore Ltd, Abingdon Oxfordshire, OX14 4RX, UK.
Br J Clin Pharmacol. 2013 Aug;76(2):173-87. doi: 10.1111/j.1365-2125.2012.04475.x.
T cells are a multifaceted family pivotal in the operations of the immune system and many of its associated diseases. The pathway to understanding T cells has been marked by several pharmacological advances including the discoveries of ciclosporin, tacrolimus and the mTOR inhibitors which revolutionized transplant therapy along with providing relief for severe eczema, asthma and other immunological disorders towards the end of the last century. This article will revisit the current understanding and new developments in T cell pharmacology 10 years on from the TeGenero (TGN 1412) debacle and look at more recent successes with ex vivo antigen presenting cell incubation technologies; T cell receptor (TCR) engineering and adoptive T cell therapy both with chimaeric antibodies and also with modified T cell receptors themselves. Features of T cell biology will be explored and processes often highly unique to humans will be used to highlight what many are beginning to see as an exciting new monoclonal (T cell) frontier for drug development.
T 细胞是一个多面的家族，在免疫系统的运作及其许多相关疾病中起着关键作用。对 T 细胞的认识途径经历了几个药理学上的进展，包括环孢菌素、他克莫司和 mTOR 抑制剂的发现，这些进展彻底改变了移植治疗，并为上个世纪末的严重湿疹、哮喘和其他免疫性疾病提供了缓解。本文将回顾 T 细胞药理学的最新认识和新进展，距离 TeGenero（TGN1412）灾难已经过去了 10 年，并着眼于最近在体外抗原呈递细胞孵育技术方面的成功；T 细胞受体（TCR）工程和过继性 T 细胞疗法，包括嵌合抗体和修饰的 T 细胞受体本身。将探索 T 细胞生物学的特征，并利用人类特有的过程来突出许多人开始认为是激动人心的新单克隆（T 细胞）药物开发前沿。
